The Histone H4 Acetyltransferase NuA4 is Required for Appropriate RNA Splicing in Saccharomyces cerevisiae

Abstract

Eukaryotes undergo transcription and splicing simultaneously, allowing for coordination and regulation of these two processes. Currently, there are a few known connections between chromatin modification, which regulates transcription, and splicing found in yeast and metazoa1,2, yet there is still much to study. The NuA4 histone acetyltransferase works with Swr1 chromatin remodeling enzyme to promote transcription3–5. First, NuA4 acetylates histone H4, which is required for the recruitment of Swr1. Next, Swr1 inserts the histone variant H2A.Z, which is subsequently acetylated by NuA4. Interestingly, in Saccharomyces cerevisiae, both NuA4 and Swr1 play a key role in the transcription of the ribosomal protein genes7, which make up a large fraction of the intron containing genes. Thus, NuA4, Swr1, and H2A.Z are excellent candidates for coordinating transcription and splicing. A role for H2A.Z in splicing was recently identified6. Interestingly, data from our lab suggest that NuA4 may have functions in RNA splicing that are independent of H2A.Z deposition. Using directed genetic screens we identified positive (suppressive) interactions between splicing factor gene mutations and mutations that catalytically inactivate NuA4. Additionally, using MPE‐seq8 and RT‐qPCR we found that mutations that block the catalytic activity of NuA4 alter the splicing of a subset of RNAs. Our data suggest that NuA4 plays a role in regulating RNA splicing and we are currently performing chromatin immunoprecipitation experiments to determine whether ESA1 catalytic activity impacts the association of splicing proteins with nascent RNAs during transcription. Together, our data support a model in which NuA4 interacts with the splicing machinery to coordinate transcription and splicing.Support or Funding InformationResearch Corporation for the Advancement of Science (Cottrell College Science award no. 20186) National Institutes of Health (R15GM122026).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.